The ACURASYS trial: Neuromuscular blockade in early ARDS [Classics Series]

1. In patients with severe acute respiratory distress syndrome (ARDS), treatment with neuromuscular blockade in the first 48 hours significantly reduced 90-day and 28-day mortality when compared to placebo.

2. The group treated with the neuromuscular blocker also experienced significantly lower rates of barotrauma and there were no differences between the groups in terms of ICU-acquired paresis.

Original Date of Publication: September 2010

Study Rundown: Acute respiratory distress syndrome (ARDS) is commonly encountered in patients requiring intensive care, and is characterized by hypoxemic respiratory failure, bilateral chest infiltrates, and high mortality. While the ARMA trial had demonstrated that lung-protective mechanical ventilation was effective, no other measures had convincingly reduced mortality from ARDS at the time this study was conducted. The ARDS et Curarisation Systematique (ACURASYS) trial was conducted to evaluate if early treatment of ARDS with cisatracurium besylate, a neuromuscular blocker, would significantly improve outcomes.

In summary, treating patients with severe ARDS with neuromuscular blockade in the first 48 hours of onset significantly reduced 90-day mortality and 28-day mortality. Patients receiving neuromuscular blockade also experienced significantly lower rates of barotrauma, while there were no differences between the two groups in the rate of ICU-acquired paresis. One criticism of the study is that the authors did not use train-of-four stimulation to assess the extent of neuromuscular blockade, and based their dosing solely on a previous smaller study.

Click to read the study in NEJM

In-Depth [randomized controlled trial]: A total of 340 patients from 40 intensive care unit (ICUs) from across France were enrolled and randomized as part of this trial. Patients were eligible for the trial if they were receiving invasive mechanical ventilation, had acute hypoxemic respiratory failure, and met severe ARDS criteria (i.e., PaO₂:FiO₂ ratio <150 with positive end-expiratory pressure ≥5 cm H₂O, tidal volumes between 6-8 mL/kg, bilateral pulmonary infiltrates, non-cardiogenic edema) for ≤48 hours. Exclusion criteria included age <18 years, treatment with neuromuscular blockade at enrolment, known pregnancy, increased intracranial pressure, severe chronic liver disease, bone-marrow transplantation or chemotherapy-induced neutropenia, and pneumothorax, amongst others. Enrolled patients were randomized to receive cisatracurium besylate (i.e., 15 mg rapid infusion, followed by continuous infusion of 37.5 mg/hour) or placebo infusion. The primary outcomes were in-hospital and 90-day mortality. The secondary outcomes included 28-day mortality, the rate of barotrauma, and the rate of ICU-acquired paresis.

The only baseline difference between the two groups was a significantly lower PaO₂:FiO₂ ratio in the cisatracurium group, as compared to the placebo group (p=0.03). After adjusting for baseline PaO₂:FiO₂, treatment with cisatracurium significantly reduced 90-day mortality as compared with placebo (HR 0.68; 95%CI 0.48-0.98). Moreover, 28-day mortality was also significantly lower in the cisatracurium group (ARR -9.6%; 95%CI -19.2 to -0.2%). Patients in the cisatracurium group also experienced significantly lower rates of barotrauma (RR 0.43; 95%CI 0.20-0.93) and ICU-acquired paresis (p=0.51) when compared to patients receiving placebo.

Image: PD

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